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Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing

Wound healing is impaired in the diabetic status, largely attributable to diabetes-associated angiopathy. Pericytes play critical roles in the stabilization of the formed vessels. The loss and dysfunction of pericytes have been reported in inflammation during diabetes and associated with the patholo...

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Autores principales: Jin, Wenxv, Chen, Xiong, Kong, Lingguo, Huang, Chongqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381706/
https://www.ncbi.nlm.nih.gov/pubmed/35990676
http://dx.doi.org/10.3389/fimmu.2022.960925
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author Jin, Wenxv
Chen, Xiong
Kong, Lingguo
Huang, Chongqing
author_facet Jin, Wenxv
Chen, Xiong
Kong, Lingguo
Huang, Chongqing
author_sort Jin, Wenxv
collection PubMed
description Wound healing is impaired in the diabetic status, largely attributable to diabetes-associated angiopathy. Pericytes play critical roles in the stabilization of the formed vessels. The loss and dysfunction of pericytes have been reported in inflammation during diabetes and associated with the pathology of diabetic angiopathy. However, a practical approach that targets inflammatory pericytes to improve diabetic wound healing is lacking. In the current study, we showed that the inflammatory pericytes from wound skin of diabetic patients were impaired in growth potential and underwent oxidative stress and apoptosis. Expression of antioxidant gene oxidation resistance protein 1 (OXR1) specifically in pericytes through an adenovirus carrying OXR1 under a pericyte-specific neuron glia antigen-2 (NG2) promoter (AV-NG2p-OXR1) relieved the oxidative stress, reduced the apoptosis, and recovered the growth potential in diabetic pericytes. Moreover, expression of OXR1 in diabetic pericytes retrieved their potential of both suppressing the migration of co-cultured HUVECs and inducing cell aggregates at the branching points, indicating a functional recovery. In vivo gene therapy using this AV-NG2p-OXR1 to DB/DB mice, the mouse model for type 2 diabetes, significantly improved wound healing, likely through enhancing blood flow at the wound rather than increasing vessel density. Together, our data suggest that gene therapy targeting inflammatory pericytes may improve diabetes-associated impaired wound healing.
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spelling pubmed-93817062022-08-18 Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing Jin, Wenxv Chen, Xiong Kong, Lingguo Huang, Chongqing Front Immunol Immunology Wound healing is impaired in the diabetic status, largely attributable to diabetes-associated angiopathy. Pericytes play critical roles in the stabilization of the formed vessels. The loss and dysfunction of pericytes have been reported in inflammation during diabetes and associated with the pathology of diabetic angiopathy. However, a practical approach that targets inflammatory pericytes to improve diabetic wound healing is lacking. In the current study, we showed that the inflammatory pericytes from wound skin of diabetic patients were impaired in growth potential and underwent oxidative stress and apoptosis. Expression of antioxidant gene oxidation resistance protein 1 (OXR1) specifically in pericytes through an adenovirus carrying OXR1 under a pericyte-specific neuron glia antigen-2 (NG2) promoter (AV-NG2p-OXR1) relieved the oxidative stress, reduced the apoptosis, and recovered the growth potential in diabetic pericytes. Moreover, expression of OXR1 in diabetic pericytes retrieved their potential of both suppressing the migration of co-cultured HUVECs and inducing cell aggregates at the branching points, indicating a functional recovery. In vivo gene therapy using this AV-NG2p-OXR1 to DB/DB mice, the mouse model for type 2 diabetes, significantly improved wound healing, likely through enhancing blood flow at the wound rather than increasing vessel density. Together, our data suggest that gene therapy targeting inflammatory pericytes may improve diabetes-associated impaired wound healing. Frontiers Media S.A. 2022-08-03 /pmc/articles/PMC9381706/ /pubmed/35990676 http://dx.doi.org/10.3389/fimmu.2022.960925 Text en Copyright © 2022 Jin, Chen, Kong and Huang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author (s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Jin, Wenxv
Chen, Xiong
Kong, Lingguo
Huang, Chongqing
Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing
title Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing
title_full Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing
title_fullStr Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing
title_full_unstemmed Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing
title_short Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing
title_sort gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381706/
https://www.ncbi.nlm.nih.gov/pubmed/35990676
http://dx.doi.org/10.3389/fimmu.2022.960925
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